A large number of studies have indicated that behavioral and emotional factors have an important role in cardiovascular disease. The convergence of limbic and autonomic information in the insular cortex suggests that it is a likely site for integrating behavioral-autonomic mechanisms. Stroke patients are also known to develop a number of cardiovascular abnormalities. Recent evidence suggests that the insular cortex may be the central site responsible for the cardiovascular aberrations associated with stroke. The goal of the proposed project is to explore the insular cortex of the rat for cardiovascular and other autonomic responses and to determine, using anatomic and physiological methods, the efferent pathways to autonomic preganglionic nuclei which are responsible for mediating these responses. In the first set of experiments, the insular cortex will systematically explored using a microstimulation method to elicit cardiovascular and other autonomic responses. In the second set of experiments, the antergrade tracer phytohemagglutinin-L will be used to determine the efferent connections of discrete areas within the insular cortex from which characteristic autonomic responses can be obtained. In the third set of experiments, extracellular recordings will be made from neurons in subcortical and autonomic sites in the insular cortex. It will be determined if these units receive input from the insular cortex and if they project directly to autonomic prepanglionic nuclei. In addition, they will be tested for their response to baro- and chemoreceptor afferent information. The fourth set of experiments will use synaptic blockade with cobalt injections and electrolytic lesions in subcortical sites identified in the previous experiments, to block the autonomic responses elicited from the insular cortex. These studies should define specific areas in the insular cortex from which characteristic cardiovascular and autonomic responses originate and determine the efferent pathways from these areas. The role of subcortical autonomic nuclei in integrating the insular responses will be assessed and the subcortical sites which are critical for mediating these responses will be determined.